Diabetes mellitus, or simply diabetes, is a metabolic condition, or combination of conditions, in which an individual displays high concentrations of blood glucose. The condition is caused either by insufficient production of insulin within the body or by the failure of cells to respond properly to the insulin that is produced.
Diabetes is one of the leading causes of death and disability in the United States and in other developed countries. Diabetes is associated with long-term complications affecting almost every part of the body. For example, the disease can lead to blindness, heart and blood vessel disease, stroke, kidney failure, amputations, and nerve damage. Diabetes affects approximately 8 percent of the United States population, and the total cost of diabetes in the United States alone is estimated to approach $200 billion.
Diabetes is most typically classified as either type 1 diabetes (also referred to as insulin-dependent diabetes or juvenile diabetes), wherein the subject fails to produce sufficient insulin, type 2 diabetes (also referred to as non-insulin-dependent diabetes, adult-onset diabetes, or obesity-related diabetes), wherein the subject fails to respond properly to insulin, or gestational diabetes, wherein the condition develops in women late in pregnancy.
Type 1 diabetes results from the loss of insulin-producing beta cells in the pancreas, generally due to an autoimmune response against the beta cells. The cause of the autoimmune response is not known, but it is believed that genetic and environmental factors, including the possible involvement of viruses, could be involved. Symptoms of type 1 diabetes include increased thirst and urination, hunger, weight loss, blurred vision, and extreme fatigue. Although it can appear at any age, type 1 diabetes most frequently develops in children and young adults. Roughly 5 to 10 percent of all diabetes cases are considered type 1 diabetes.
Type 2 diabetes is the most common form of diabetes, accounting for 90 to 95 percent of all cases of diabetes. Type 2 diabetes is generally associated with older age, obesity, family history, previous history with gestational diabetes, and physical inactivity. It is also more prevalent in certain ethnicities. Type 2 diabetes is also referred to as insulin-resistant diabetes because the pancreas is usually able to produce sufficient amounts of insulin, but the body fails to respond properly to that insulin. As with type 1 diabetes, blood glucose levels in individuals suffering from type 2 diabetes increase, and the body is unable to metabolize the blood glucose efficiently. The symptoms of type 2 diabetes generally develop more slowly than those of type 1 diabetes. The symptoms include fatigue, frequent urination, increased thirst and hunger, weight loss, blurred vision, and slow healing of wounds or sores. In some cases, no symptoms are evident.
Gestational diabetes occurs in approximately 3 to 8 percent of pregnant women in the United States, generally developing late in the pregnancy. The disease typically disappears after birth of the baby, but women who have experienced gestational diabetes are significantly more likely to develop type 2 diabetes within 5 to 10 years than those who have not. Women who maintain reasonable body weight and are physically active after suffering from gestational diabetes may be less likely to develop type 2 diabetes than those who do not. As with type 2 diabetes, gestational diabetes occurs more frequently among women with a family history of diabetes and also in certain ethnic groups.
Since the discovery of insulin over 80 years ago, diabetes, particularly type 1, or insulin-dependent diabetes, has been a somewhat treatable condition. The combination of a proper diet, physical activity, and insulin injection, together with the monitoring of blood glucose levels using portable meters, allows the management of type 1 diabetes. For type 2 diabetics, healthy eating, physical activity, and monitoring blood glucose levels are also important. In some cases, drug therapies can be used to control blood glucose levels in these patients.
Other approaches to the treatment of diabetes are also desirable. For example, it has been shown that bariatric surgery for the treatment of gross obesity may also cure obesity-related diabetes. It is thought that this surgery, which involves bypass of at least a portion of the small intestine, could cause the surgical ablation of gastric inhibitory polypeptide (GIP)-secreting intestinal K cells. Flatt (2007) Diab. Vasc. Dis. Res. 4, 150. As a result, circulating levels of GIP, which is thought to play a key role in lipid metabolism and fat deposition, are decreased.
Furthermore, although the underlying cause of type 1 diabetes remains unknown, a defect in a subset of sensory neurons that innervate the pancreas may play a role in initiating a series of events leading to local inflammation, destruction of islet cells in the pancreas, and autoimmune (type 1) diabetes. Razavi et al. (2006) Cell 127, 1123. In individuals with the defect, insulin secretion by beta cells fails to properly stimulate sensory neurons expressing a hypofunctional, polymorphic capsaicin receptor (TRPV-1=transient receptor potential vanilloid-1) to release neuropeptides. Suboptimal local levels of neuropeptides lead to insulin resistance and beta cell stress and ultimately an autoimmune response against the beta cells. Identifying methods to control these pathways could thus provide novel approaches for treating or preventing diabetes.
Another health problem of major importance, particularly in the developed world, is obesity. Obesity is a complex, multifactorial and chronic condition characterized by excess body fat. Obesity results from an imbalance between energy expenditure and caloric intake. Although the causes of this imbalance are not completely understood, genetic and/or acquired physiologic events and environmental factors are important. The adverse health effects of obesity, and more particularly morbid obesity, have become well-known in recent years. Such adverse health effects include, but are not limited to, cardiovascular disease, diabetes, high blood pressure, arthritis, and sleep apnea. Generally, as a patient's body mass index (BMI) rises, the likelihood of suffering the adverse health effects of obesity also rises.
Often, surgery has been the only therapy that ensures real results in patients who have BMI values close to, or in excess of, 40 kg/m2. Modern surgical procedures generally entail either (1) the reduction of gastric compliance, with the aim of limiting the subject's ability to ingest food, or (2) the reduction of the food absorption surface by shortening or bypassing part of the digestive canal. In some cases, both aims are sought through the same surgical procedure. The risk and invasiveness factors of currently available surgeries are often too great for a patient to accept to undergo surgical treatment for treatment of obesity. Accordingly, there is a need for less invasive, yet effective treatment procedures for the morbidly obese. Also, since the current surgical procedures are currently indicated only for those patients having a BMI of 40 or greater, or 35 or greater, when co-morbidities are present, it would be desirable to provide a less invasive procedure that would be available for slightly less obese patients, e.g., patients having a BMI of 30 to 35 who are not indicated for the currently available surgical procedures.
U.S. Patent Application Publication No. 2008/0275445 reports devices for use in ablating tissue in the wall of luminal organs of the gastrointestinal tract. See also U.S. Pat. No. 7,326,207. Such devices are purportedly useful in the treatment of pathophysiological metabolic conditions, such as type 2 diabetes, insulin resistance, obesity, and metabolic syndrome, but the effectiveness of such treatments has not been demonstrated.
U.S. Patent Application Publication No. 2004/0089313 reports systems and methods for treating obesity and other gastrointestinal conditions by targeting the stomach. In particular, the methods purportedly cause tightening of the pyloric sphincter or alteration of the receptive relaxation of stomach muscles. The treatments include ablation of stomach tissue and, in some cases, injection of a cytokine or a vanilloid-containing compound into stomach tissue. The effectiveness of these treatments has not, however, been reported.
Given the widespread and growing significance of diabetes and obesity throughout the population, there is clearly a strong need for additional methods of treating and preventing these diseases.